Localization of objects within a conductive volume

ABSTRACT

An example method includes applying a localization signal to a source electrode positioned within a conductive volume and a ground electrode at a known location. Electrical activity is sensed at a plurality of sensor electrodes distributed across an outer surface of the conductive volume. The locations of each of the sensor electrodes and the location of the ground electrode being stored in memory as part of geometry data. The electrical activity sensed at each of the sensor electrodes is stored in the memory as electrical measurement data. The method also includes computing a location of the source electrode by minimizing a difference between respective pairs of source voltages determined for the plurality of sensor electrodes. The source voltage for each of the sensor electrodes is determined based on the electrical measurement data and the geometry data.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/867,716, filed Sep. 28, 2015, and entitled LOCALIZATION OF OBJECTSWITHIN A CONDUCTIVE VOLUME, which claims the benefit of priority to U.S.provisional patent application No. 62/056,214, filed Sep. 26, 2014, andentitled NAVIGATION OF OBJECTS WITHIN THE BODY, which is incorporatedherein by reference in its entirety.

TECHNICAL FIELD

This disclosure relates to navigation of objects within a body.

BACKGROUND

This section provides background information related to the presentdisclosure and is not necessarily prior art.

A navigation system can locate an object within a volume. For example, anavigation system can be used to track an instrument during a procedure,such as a surgical procedure. Various systems can be used to trackinstruments including electromagnetic systems, optical systems, magneticsystems acoustic systems, and the like. However, existing techniquestend to be insufficiently accurate or are incapable of real-timeapplications.

SUMMARY

This disclosure relates to localization of objects within a conductivevolume.

As one example, a system includes a plurality of sensors configured tosense electrical activity at locations distributed across an outersurface of a conductive volume, locations of each of the plurality ofsensors being predetermined with respect to a spatial coordinate systemand stored in memory as geometry data. A source electrode is positionedwithin the conductive volume at a location that is to be determined. Asignal generator is to supply electrical energy to the source electrode,corresponding to a source voltage, which generates an electric field. Alocation calculator is configured to compute the location of the sourceelectrode by minimizing a difference between source voltages determinedfor multiple pairs of the plurality of sensors. The source voltage foreach pair of the plurality of sensors being determined based on sensormeasurements for each respective one of the plurality of sensors inresponse to corresponding electric field and the geometry data.

As another example, a method includes applying a localization signal toa source electrode positioned within a conductive volume at a locationthat is to be determined and a ground electrode on an outer surface ofthe conductive volume a location of ground electrode being known.Electrical activity is sensed at a plurality of sensor electrodesdistributed across the conductive volume. The locations of each of thesensor electrodes and the ground electrode being stored in memory aspart of geometry data. The electrical activity sensed at each of thesensor electrodes in response to the applied localization signal isstored in memory as electrical measurement data. The method alsoincludes computing the location of the source electrode by minimizing adifference between source voltages determined for multiple pairs of theplurality of sensor electrodes. The source voltage for each of thesensor electrodes is determined based on the electrical measurement dataand the geometry data.

As yet another example, a computer-readable medium stores data andinstructions executable by a processor. The data includes geometry datarepresenting locations of each of a plurality of sensors and measurementdata representing sensed electrical measurements for each of theplurality of sensors of a corresponding electric field generated inresponse to applying a field of a source electrode within the conductivevolume. The instructions comprise a location calculator to compute aposition for location of the source electrode within the conductivevolume by minimizing a difference between source voltages determined formultiple pairs of the plurality of sensors, the source voltage for eachof the plurality of sensors being determined based on the measurementdata including sensor measurements for each respective one of theplurality of sensors in response to the corresponding electric field andthe geometry data.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an example of a system to determine a location of sourcewithin a conductive volume.

FIG. 2 depicts an example of a volume conductive media which is mostlyresistive, and electrical stimulation being injected by a unipolar lead.

FIG. 3 depicts an example of a circuit approximating the flow ofelectrical current through the volume conductor of FIG. 2.

FIG. 4 depicts an example of a schematic cross-sectional view of bodydemonstrating relationships between one-to-one pairings of externalsensors and between an internal signal source in the heart and anexternal sensor.

FIG. 5 depicts an example of a schematic cross-sectional view of bodydemonstrating relationships between a reference sensor paired with eachof an arrangement of other external sensors.

FIG. 6 depicts an example of a navigation and mapping system.

FIG. 7 is a flow diagram depicting a method of localization of a sourcewithin a conductive volume.

DETAILED DESCRIPTION

This disclosure relates to systems and methods to determine location ofan object within a volume conductor. For example, the approach can beimplemented by using an arrangement of sensors distributed across thevolume conductor (e.g., invasively and/or non-invasively across thevolume) for navigation and/or localization of an object, such as acatheter. By knowing, a priori, the spatial position for each of thesensors with respect to a coordinate system of the volume conductor, thespatial position of a source object can be ascertained with respect tothe same coordinate system based on electrical signals that are emittedfrom the object and measured by the sensors. For example, the unknownlocation of the source object can be determined by minimizing adifference between source voltages determined for different pairs of theplurality of sensors. The source voltage for each pair of sensors isdetermined based on sensor measurements of a respective one of theplurality of sensors in response to the corresponding electric field(which is generated in response to supplying electrical energy to thesource electrode) and the geometry data. As a result, an absolutespatial position of the object can be determined with a high level ofaccuracy, such as for localization of the object or to facilitate itsnavigation to a desired site within the body.

The computed location can be further employed to display graphically anindication of position for the source, such as can correspond to one ormore electrodes on a catheter or other probe. A collection of locationinformation can be collectively displayed to represent a surface orincorporated in a graphical map of patient anatomy or generic model byco-registering the determined location coordinates with anatomicalgeometry (e.g., for a given patient or a generic model).

FIG. 1 depicts an example of a system 10 for localizing a source 12 thatis positioned within a conductive volume 14. The conductive volume canbe a patient's body or some other conductive media in which the sourceis being localized. As disclosed herein, the source 12 can be a sourceelectrode or multiple electrodes that can be positioned within and, insome cases, be moveable within the volume 14. For example, the source 12is an electrode that is carried on a surface of a probe, such as acatheter or other apparatus.

A plurality of sensors 18 can be positioned across the conductive volume14, which may include sensors on an external surface of the conductivevolume 14 and/or within the volume. The locations of the sensors 18 areknown in a corresponding coordinate system that describes the spatialgeometry of such sensors in three-dimensional space. The locations ofthe sensors 18 can be determined from imaging and/or other means (e.g.,digitizer, self-discovery or using one set of the sensors to detectanother set of the sensors). As one example, the sensors 18 cancorrespond to a high-density arrangement of surface sensors that aredistributed over a portion of exterior surface of the conductive volume14 for measuring electrical activity (e.g., electrocardiograms (ECGs) ofa patient's heart). An example of a non-invasive sensor array that canbe used is shown and described in International application No.PCT/US2009/063803, filed 10 Nov. 2009, which is incorporated herein byreference. Other arrangements and numbers of sensors 164 can be used.Additionally or alternatively, in other examples, the sensors 18 may besensor electrodes positioned within the conductive volume at respectivelocations known in the coordinate system.

A signal generator 16 can be electrically connected with the sourceobject 12 for supplying electrical energy to the object, correspondingto a source voltage. The supplied electrical energy (e.g., current orvoltage) generates the corresponding electric field in the conductivevolume that can be measured by the sensors 18. An electrical circuitpath can extend from the signal generator and the conductive volume 14.For example, the circuit path extends from the signal generator 16 tothe source 12, from the source to a corresponding ground electrode,which is on the surface of the conductive volume at a known position,and from the ground electrode back to the signal generator.

The sensors 18 each provide sensor signals to an electric measurementsystem 20 representing electrical activity measured by each respectivesensor. The electrical measurement system 20 is configured to receivesignals from each of the sensors 18. While demonstrated as separate fromthe sensors 18 in the example of FIG. 1, the electrical measurementsystem 20 can include the sensors 18, which can include non-invasivelyand/or invasively positioned at known fixed locations sensors across theconductive volume (e.g., a patient's body). In some examples, one ormore invasive sensors can be movable within the patient's body, such ascan be attached to a probe (e.g., a catheter). The source electrode 12that is being localized can be mounted to the same probe object and at afixed, known relative position as such invasive sensors, such as toenable the position of the probe object and its complement of one ormore sensors to also be determined by the location calculator 30.

The electric measurement system 20 thus can perform processing of thesensor signals (e.g., including filtering and/or amplification) toprovide corresponding electric measurement data 22. The electricmeasurement data 22 can be stored in the corresponding memory. Theelectrical measurement data 22 thus provides signal measurements fordiscrete known locations based upon the sensed electrical signals byeach of the sensors 18 implemented by the system. Each electricalmeasurement in the data 22 can include time stamps, such as from asystem clock. The localization signal applied by the signal generator 16can also be indexed to the same time base to enable synchronization ofthe measurement data with the signal being localized.

The system also includes geometry data 24, which is demonstrated asincluding sensor location data 26 and anatomical data 28. The sensorlocation data 26 represents location of each of the sensors 18 that hasbeen determined with respect to a spatial coordinate system. The spatialcoordinate system can be registered with structural features of theconductive volume. For example, the sensor locations 18 can beregistered in a spatial coordinate system in which the patient's anatomyhas also been registered, such as to enable determining coordinates ofthe object 12 with respect to the spatial coordinate system. Theanatomical data 28 can include geometry information associated with theconductive volume 14 including the surface geometry of the outer surfacethereof to which the sensors 18 have been affixed as well as boundariesof internal features within the conductive volume. The anatomical data28, for example, represents the boundary of the heart, including one ormore of epicardial or endocardial surfaces thereof.

The geometry data 24 can be generated in various ways. As one example,the geometry data can be provided based on imaging data of theconductive volume while sensors 18 are applied to its surface. An imageprocessing system can process the acquired image data from the imagingsystem (e.g., corresponding to one or more imaging modality) and providethe geometry data 18. The image processing can include segmentation ofanatomical features from the digital image data, which can identifystructural boundaries and fiducial markers of patient anatomy and sensorlocations within the image space. Examples of imaging modalities includeultrasound, computed tomography (CT), 3D Rotational angiography (3DRA),fluoroscopy, magnetic resonance imaging (MRI), X ray, positron emissiontomography (PET), and the like. Such imaging can be performed separately(e.g., before or during the measurements) utilized to generate thegeometric data.

As another example, the sensors can be configured to determine theirlocation via self-discovery. For instance, a specific programmedsequence of current/voltage can be applied among electrodes, and thespatial distribution of the electrodes, with respect to each other or aneutral point, can be computed. This ‘self discovery’ lead set could beregistered to the CT or into another three-dimensional coordinate systemusing a registration technique, such as disclosed herein. Additionallyor alternatively, the geometrical location of the sensors can bedetermined via direct registration (e.g., digitization using a digitizerdevice or recording manual physical measurements).

The system 10 also includes a location calculator 30 configured tocompute location data 32 that represents a position for the source 12based on the electrical measurement data 22 and the geometry data 24.The location data 32 thus specifies the location of the object 12 in acorresponding spatial coordinate system, which can be registered to theconductive volume 14. For example, the location calculator 30 implementsa minimization function 34 configured to minimize a difference betweensource voltage values determined for each of a plurality of pairs of thesensors 18.

The minimization function 34 can be programmed to compute a respectivesource voltage for the object 12 based upon the sensor measurementsprovided in electrical measurement data for each respective one of theplurality of sensors 18 in response to a corresponding electric fieldthat is generated by the source 12 when supplied electrical energy fromthe signal generator 16. The minimization function 34 also utilizessensor location data for each of the pairs of sensors as part of eachsource voltage calculation. The minimization function 34 is configuredto compute the source location in a corresponding spatial coordinatesystem based on the electrical measurement data 22 from each selectedpair of sensors and associated location data 26 for the selectedsensors. As disclosed herein, the selection of each sensor pairs can becontrolled based on the geometry data 24, the electrical measurementdata 22, channel integrity and/or be in response to a user selection(e.g., via user input).

Since the plurality of the sensors 18 are distributed around theconductive volume 14 the electric measurement data 22 for a givenelectrical signal supplied by the signal generator 16 are temporally andspatially consistent. Thus, the location calculator 30 can compute theposition based on the electrical measurement data 22 that has beenacquired concurrently for each of the sensors 18 in response to thecorresponding electric field that is generated in response to the signalsupplied by the signal generator 16 to the source. A control signal canactivate the signal generator 16 to periodically (or intermittently)supply the source signal. The electrical measurement system can storethe electrical measurement data 22 with time stamps, such as from asystem clock. The localization signal applied by the signal generatorcan also be indexed to the same base to enable synchronization of themeasurement data 22 with the signal being localized. The measurementdata record can also include a field specifying to which sensor thesensed measurement belongs. The sensor identifying information can alsobe used to access the location data 26 for each respective sensor.

The location calculator 30 includes a sensor selector 38 to select andretrieve measurement data 22 for each respective pair of the sensors 18for use by the minimization function 34. Of the available set of sensors18 (e.g., at least 3, such as greater than 20 sensors), for example, thesensor selector 38 selects three or more different pairs of the sensorsfrom the plurality of available sensors 18. In some examples, the sensorselector can select each available pair of sensors for use in computingthe location of the source 12. In other examples, the sensor selector 38selects a proper subset of the available pairs of the sensors 18.

By way of example, the sensor selector 38 selects the respective sensorsin response to user input (e.g., via a graphical user interface). Forinstance, a user can specify one or more sensors to be included orexcluded from the minimization function 34. Alternatively oradditionally, the sensor selector 38 can be programmed to automaticallydetermine which pairs of sensors to utilize when executing theminimization function 34. For instance, to increase the sensitivity ofdetection of electrical fields, the sensor selector 38 can choose anoptimal subset of electrodes based on other various characteristics, forexample, lead vector, solid angle subtended by each field (sensor) pointon the body surface. The respective pairs of sensors utilized incalculations performed by the minimization function 34 can be selectedin response to a calibration engine 36 that is a preprogrammed methodfor calibrating the location calculator 30 including the minimizationfunction 34. The calibration engine 36 can drive the sensor selector 38based on the electrical measurement data 22 and/or geometry data 24.

As one example, the calibration engine 36 is configured to group theplurality of sensors 18 into two or more subsets of sensors. Thelocation calculator 30 thus can apply the minimization function 34 tocompute the source location by minimizing the difference between sourcevoltages (e.g., represented by the electrical measurement data 22) thatcan be determined for each respective pair of sensors in each of thesubsets that have been identified. If more than two subsets of sensorsare identified by calibration engine 36, location calculator 30 cancompute the system by aggregating the position values that have beenseparately computed for each of the respective subsets of sensors.

As an example, the minimization function 34 can be configureddifferently (e.g., employ different conductivity or resistivity values)for each subset of sensors. The different groups of sensors can residein different regional volume or pairs of sensors that form each groupcan be interspersed across the surface of the volume 14. In this way,the minimization function 34 can be tailored according to the uniquespatial and/or electrical characteristics in each group of the sensors.

As a further example, the calibration engine 36 can include an impedancecalculator 40 configured to compute impedance for at least a portion ofthe conductive volume 14 based upon the electrical measurement data 22and/or geometry data. For example, sensors 18 can further be configuredto apply fields to the surface of the conductive volume which can bedetected by other sensors distributed thereon. By applying fields andsensing respective fields pass the conductive volume 14 an indication ofimpedance throughout the volume can be ascertained. Thus, the impedancedetermined through corresponding portions of the conductive volume canbe utilized by the sensor selector 38 to identify respective groups ofthe sensors 18, such as according to the relative impedance betweenrespective pairs of sensors.

As yet another example, the calibration engine 36 includes a homogeneitycalculator 42 to determine indication of homogeneity or inhomogeneity ofimpedance throughout the volume 14. For example the homogeneitycalculator 42 can determine the indication of homogeneity (orinhomogeneity) within the conductive volume between respective pairs ofthe sensors 18. The indication of homogeneity can be determined as arelative index of homogeneity that can be determined for the conductivevolume residing between respective pairs of the sensors 18. For example,the homogeneity calculator computes the index of homogeneity based onthe impedance values computed by the impedance calculator 40 fordifferent pairs of sensors across the volume 14. As disclosed herein,the impedance values can be based on measuring electricalcharacteristics between pairs of sensors (e.g., part of measurement data118). The sensor selector 38 thus can employ relative indication ofhomogeneity to group the sensors into two or more subsets of sensors.The resulting pairs of sensors within each group can thus be consideredto have a sufficient level of homogeneity within the conductive volumebetween the pairs to improve computational accuracy of the minimizationfunction 34, such as disclosed herein.

By way of further example, FIGS. 4 and 5 demonstrate examples of but twoapproaches that can be utilized to characterize impedance and/orhomogeneity of a conductive volume 14 based on electrical measurement ofapplied electric fields (e.g., referred to as calibration fields). Thecalibration fields could be bipolar (e.g. two poles of the catheter) orunipolar (between a source and a neutral reference or ground electrode).Each of the examples of FIGS. 4 and 5 demonstrate a cross-sectional viewof the volume conductor, demonstrated at 80 (corresponding to volume 14of FIG. 1), which depicts the external surface boundary of the volume(e.g., the patient's skin) 82 as well as an internal structure (e.g.,the patient's heart) 84 along a virtual plane. Additionally, a pluralityof electrodes 86 (corresponding to sensors 18 of FIG. 1) are disposed onthe surface 82, such as evenly distributed around the volume. In theexample of FIG. 4, an internal electrode 88 is also depicted within thevolume conductor, such as may reside within or otherwise contact on theinternal structure 84.

In some examples, the surface electrodes 86 are configured for bothmeasuring and delivering electric fields from their noninvasive (e.g.,external) location into the body. The same electrodes 86 used forsensing electrical activity from the body surface thus can be used todeliver the electric fields. In other examples, different electrodes 86can be positioned at the same of different predetermined locations asthe sensing electrodes to deliver the electric fields between respectivepairs of electrodes 86, 88. Thus, a signal generator 90 can applyelectrical field (e.g current or voltage) can be injected through one ormore sets of electrodes 86, 88.

The electrodes 86, 88 thus can be used as sense electrodes to detect anapplied electric field from various locations around or near the thorax,which can be used by the calibration engine 36 (e.g., includingcalculators 40 and/or 42) to help characterize the thoracic impedanceand/or homogeneity of the volume. The values computed by calculators 40and/or 42 can be determined in real-time computations and/or be storedin a look up table for compensating for impedance related errors insolving the minimization function 34. location.

In the example of FIG. 4, the signal generator 90 applies the electricalenergy (e.g., AC signal having a prescribed frequency) between a pair ofelectrodes that include both a non-invasive external electrode 86 and aninternal electrode 88. In the example of FIG. 5, the signal generator 90applies the electrical energy between a pair of non-invasive externalelectrodes 86 to generate a corresponding electric field. The fieldinjection (e.g. current or voltage) and sensing from differentpairs/sets of electrodes can be implemented to occur in a pre-programmedtime sequence, or concurrently but with different frequencies fordifferent sets of electrodes. The injected calibration field can be adipolar or unipolar field, and be injected between any pairs ofelectrodes, invasive or non-invasive. For instance, current/voltage canbe injected between pairs or electrodes through time/frequency divisionmultiplexing and the resulting fields can be sensed by other pairs ofsensors 86.

The resulting electric field that is generated can be measured (e.g. ascurrent or voltage) at other sensor electrodes 86 on the body surface,which sensed field can be employed by impedance calculator 40 tocharacterize impedance through the conductive volume 14, such as betweenrespective electrode pairs. Additionally or alternatively, the resultingfield can be measured and used by the homogeneity calculator 42 tospecify homogeneity across the volume.

Additionally or alternatively, referring back to FIG. 1, the impedanceinhomogeneity of the conductive media between any pair of sensors 18 canbe determined from imaging data, such as CT or MRI images (e.g.,represented as part of the anatomical data 28). The inhomogeneity (orhomogeneity) can be determined by the calibration engine 36 so that thesource voltage computations implemented by the minimization function 34for each pair of sensors are adjusted accordingly to account for thecorresponding level of inhomogeneity.

In some examples, the location calculator 30 employs channel integritydata 44 to determine if data 22 and 24 for any of the sensors 18 shouldbe omitted from the localization methods. For example, a channeldetector 46 can process the electrical measurement data 22 and/orreceives feedback information from the electrical measurement system 20to provide the channel integrity data 44 indicating which channels mayprovide erroneous results. The channel detector 46 can implement thefunctions and methods corresponding to channel integrity detectionsystem disclosed in respect to U.S. Patent Pub. No. 2013/0304407, whichis incorporated herein by reference. Other channel integrity analysisapproaches could also be utilized. For example, short circuits, opencircuits or other sensing issues can be utilized to identify or generatethe channel integrity data 44. The sensor selector 38 thus can identifyand remove bad channels (e.g., flag with metadata) and provide theremaining subset of sensors 18 as the available asset of correspondingelectrical measurement data 22 and associated geometry data 24 to beutilized by the location calculator 30 in computing the location data32.

The location data 32 thus can represent the computed location as anabsolute (or relative) position in such given coordinate system at oneor more time instances as a function of the electrical measurement data22 that has been synchronized with applied localization signal (e.g.,aligning data using associated time stamps). By repeating thelocalization over time, the movement of the source object 12 (e.g.,corresponding to a probe or other movable object) may be tracked overtime, such as represented by a time sequence of the location data 32. Insome examples, the location data 32 for each tracked probe can beaveraged over time to provide a smooth and robust display of thesource's location. The averaging can also adopt other prior informationsuch as the adjacent probe distance or the like. The location data 32thus can be utilized to generate a visualization of the source location,such as can be provided in a graphical map that includes the patient'sanatomy.

The location calculator 30 thus generates the location data 32 torepresent the location of the object 12 within a given coordinate system(e.g., based on the geometry data 24). The location data 32 thus canrepresent the computed location as an absolute position in such givencoordinate system at one or more time instances as a function of theelectrical measurement data 22 that has been synchronized with appliedlocalization signal (e.g., aligning data using associated time stamps).By repeating the localization over time, the movement of the sourceobject 12 (e.g., corresponding to a probe or other movable object) maybe tracked over time, such as represented by a time sequence of thelocation data 32. In some examples, the location data 32 for eachtracked probe can be averaged over time to provide a smooth and robustdisplay of the probe's location. The averaging can also adopt otherprior information such as the adjacent probe distance or the like. Thelocation data 32 thus can be utilized to generate a visualization of thelocation, such as can be provided in a graphical map that includes thepatient's anatomy.

As a further example, FIG. 2 depicts a configuration of a localizationsystem 50 that includes a volume of conductive media 52, which is mostlyresistive (e.g., corresponding to conductive volume 14). Asdemonstrated, a plurality of sensor electrodes E1, E2, E3 through E_N(where N is a positive integer denoting the number of sensor electrodes.The sensor electrodes E1, E2, E3 through E_N can be distributedsubstantially evenly across an external surface of the conductive volume52. The number N of electrodes is at least three and can be greater than20 and, in some examples, can be equal to or greater than 200electrodes. Examples of some arrangements of the sensor electrodes E1,E2, E3 through E_N that can be utilized are disclosed in theabove-incorporated PCT/US2009/063803.

A source electrode 56, which defines a unipolar lead, is positionedwithin the volume 52 at a location that is to be determined. A signalgenerator 58 is connected to provide electrical energy to the sourceelectrode 56. As illustrated in the example of FIG. 2, the signalgenerator is coupled to the source electrode 56 and a ground electrode60 that is positioned at known location on the conductive volume. Forexample, a positive terminal of the signal generator is coupled to thesource electrode and a negative terminal of the signal generator iscoupled to the ground electrode 60. While in the schematic illustrationof FIG. 2, the ground electrode and the sensor electrodes E1-E_N aredemonstrated as located on opposing sides of the volume 52, the positionof the electrodes E1-E_N will typically be distributed evenly around thevolume 52 (e.g., around the patient's thorax for cardiac localization).The ground electrode 60 can be positioned on the surface 54 of theconductive volume 52 at a user-selected location, which may bepredetermined or arbitrary. The ground electrode can be part of the samearrangement of sensors E1-E_N or it can be a separate electrode.

The signal generator 58 thus can inject electrical energy (e.g., currentor voltage) at the source electrode 56 and ground electrode 60. Theconfiguration is depicted in FIG. 2. The unipolar lead is insertedinside the conductive volume and connects to the positive output of anelectrical stimulator. The sensor electrodes E1-E_N thus are deposed onthe surface of the volume conductor 52 to measure sensed electricalactivity in response to unipolar stimulation resulting from the injectedelectrical energy. The resistance between each surface electrode and theunipolar lead is represented by R1, R2, R3 through R_N. The resistancebetween each sensor electrode E1-E_N and the ground electrode 60 isrepresented by RG1, RG2, RG3 . . . RG_N. The resistance between theunipolar lead and the ground electrode 60 is represented by R_P.

The electrical current that flows through the volume conductor 52 can becalculated by an approximation of the electrical configuration in thesystem 50, which approximation is demonstrated as the circuit 70 of FIG.3. In the circuit 70 of FIG. 3, it can be assumed that conductivity (σ)and cross-section (A) of the current going through each recordingelectrode is substantially uniform in the conductive media. Thus,according to Pouillet's Law:

R _(i) =L _(i)(σ·A)

R _(gi) =L _(g)/(σ·A)

where L_(i) is the length (e.g., (e.g., spatial distance) between theelectrode 56 and the a given one of the sensor electrodes E1-E_N, andL_(g) is the length between the recording electrode and the groundelectrode. The voltage measured from each of the sensor electrodesE1-E_N is indicated by V_(m1), V_(m2), V_(m3) . . . V_(m) _(_) _(N). Foreach electrode i, the passing through current can be expressed asfollows:

I=V ₀/(R _(i) +R _(gi))

and the voltage measurement from this electrode is:

V _(mi) =I·R _(gi)

Therefore,

$V_{mi} = \frac{V_{0} \cdot R_{gi}}{R_{i} + R_{gi}}$

Assuming σ and A are constants, the relationship for each electrode ican be rewritten as follows:

$\begin{matrix}{V_{0} = \frac{V_{mi}\left( {L_{i} + L_{gi}} \right)}{L_{gi}}} & (1)\end{matrix}$

As mentioned above, for a given electrode arrangement on the surface 54,the locations for each of the electrodes (including ground electrode 60)are known (e.g., stored in sensor location data 26). Thus, the locationr_(i) of each electrode i and the distance L_(gi) between the ithelectrode and a ground electrode are known or can be derived fromgeometry data 24. The location calculator 30 thus is configured tocompute a location of the source electrode 56, represented as r₀.

Based on Eq. (1), each electrode measurement can be used to calculatethe voltage of the source, and each source voltage, when accuratelydetermined, leads to the same quantity. Thus, the difference betweendetermined source voltages for a given pair of electrodes i and j,selected from the set of available N electrodes, should approach zero,which can be expressed as follows:

$\begin{matrix}{\left. {\frac{V_{mi}\left( {L_{i} + L_{gi}} \right)}{L_{gi}} - \frac{V_{mj}\left( {L_{j} + L_{gj}} \right)}{L_{gj}}}\rightarrow 0 \right.,{\forall{i \neq j}}} & (2)\end{matrix}$

From Eq. (2), a minimization function for computing a location for thesource r₀ can be represented as follows:

$\begin{matrix}{{E\left( r_{0}^{*} \right)} = {\min\limits_{r_{0} \in {\mathbb{R}}^{3}}{\sum\limits_{({i,j})}{{\frac{V_{mi}\left( {{{r_{i} - r_{0}}} + L_{gi}} \right)}{L_{gi}} - \frac{V_{mj}\left( {{{r_{j} - r_{0}}} + L_{gj}} \right)}{L_{gj}}}}^{2}}}} & (3)\end{matrix}$

where r_(i) and r_(j) define the locations of the ith and jthelectrodes, respectively, and r₀ is the location of the source that isbeing determined.

Eqs. (2) and (3) are based on the assumption that σ and A are constants,which may not be true in reality; however, for electrodes spatiallyresiding proximal to each other (e.g., to define a neighborhood ofnearby electrodes), the values of σ and A should be close. Therefore,the electrodes can grouped into subsets, S_(k), where k=1 . . . K (Kdenoting the number of subsets). Each subset of electrodes is consideredto reside in a respective neighborhood where the assumption that σ and Aare constants is presumed to be true for each such neighborhood. Eachsubset S_(k) can be a contiguous spatial region within the volume 52.Alternatively or additionally, the subsets of electrodes can be groupedinto respective subsets based on a determined impedance betweenrespective pairs of electrodes and/or associated homogeneity of variousregions throughout the volume (e.g., determined by respectivecalculators 40 and 42). For instance, each subset S_(k) can includepairs of electrodes determined to have an impedance and/or a homogeneityindex within a common range that has been assigned to each group. Thus,the different subsets can vary depending on patient anatomy within theportion of the volume where the source is being localized. Based on suchassumptions for each subset of electrodes, the following minimizationcan be expressed as follows:

$\begin{matrix}{{E\left( r_{0}^{*} \right)} = {\min\limits_{r_{0} \in {\mathbb{R}}^{3}}{\sum\limits_{\underset{r_{i},{r_{j} \in S_{k}}}{K = 1}}^{K}{\sum\limits_{\underset{j \in S_{k}}{i \in S_{k}}}{{\frac{V_{mi}\left( {{{r_{i} - r_{0}}} + L_{gi}} \right)}{L_{gi}} - \frac{V_{mj}\left( {{{r_{j} - r_{0}}} + L_{gj}} \right)}{L_{gj}}}}^{2}}}}} & (4)\end{matrix}$

where r_(ik) and r_(jk) are the respective locations of ith and jthelectrodes in group S_(k), k=1 . . . K, (K being a positive integerdenoting the number of groups S_(k)) and r₀ is the location of thesource.

In each of the minimization functions represented in Eqs. (3) and (4),it is understood that the voltage of source does not need to becalculated, such that there is no ill-posed inverse problem to solve.Instead, the localization calculator 30 computes the location based onthe electrode measurements and the known electrode locations (e.g., inthe absence of having to solve the inverse problem).

As lengths L_(gi) and L_(gj) are constants based on known locationsr_(i) of measurement electrodes and a fixed ground location, while|r_(i)−r₀| is not a linear operator, the minimization problem cannot besolved as linear problem. Nonetheless, various numerical methods existto solve the minimization problem presented herein, such as representedin Eqs. (3) and (4), and to calculate the position of the source basedon the measured electrical signals by the sensors and the known sensorlocations. The numerical optimization methods can include a brute-forcesearch method or an iterative method (e.g., Newton's method, gradientdescent methods, conjugate gradient method or the like.

As one example, a brute force method can involve systematically choosinginput values from within an allowed set and computing the value of thefunction 34 (e.g., from Eqs. (3) and/or (4)) according to the methodshown in the following table.

1. Partition the spatial domain within the volume conductor into a gridof voxels. 2. For each grid voxel, assume that is the location ofcatheter to be detected. The cost function (e.g., as set forth in Eq.(3) and/or Eq. (4)) can be evaluated. 3. After evaluating cost functionat all grid points, identify the grid point that provides the smallestcost function among all grid points. 4. To increase accuracy, ifdesired, resolution, another round of partitioning of the domain aroundthe point identified in 3 can be performed. Then, the method can repeat2-3. 5. The method can repeat 1-4 until a desired resolution isachieved. The desired resolution can be set in the beginning. The pointlocation corresponding to the smallest cost function at the desiredresolution grid can be stored in memory as the location datacorresponding to the source location within the volume conductor.

As mentioned above, other methods, such as Gauss-Newton's method orgradient descent methods, can be used to solve this minimization problem(e.g., from Eqs. (3) and (4)). Additionally, or alternatively, in eachof the examples localization disclosed herein (e.g., the minimizationfunctions presented in Eqs. (3) and (4)), the respective minimizationfunction can be seeded with a priori information regarding approximatelocation in the given coordinate system facilitate the determination ofthe source location. For instance, the initial location can be based ona previously determined source location in the given coordinate system.Alternatively, a location within a region of interest can be used toseed the numerical method to facilitate the minimization function.

FIG. 6 depicts an example of another system 150 that can be utilized forlocalizing one or more sources of electrical signals within a volume ofinterest, such as a patient's body 154. The system 150 can be employedin conjunction with performing diagnostics and/or treatment of apatient. In some examples, the system 150 can be implemented to generatecorresponding graphical outputs for signals and/or graphical maps for apatient's heart 152, including the position of a source, in real time aspart of a procedure (e.g., monitoring of signals during anelectrophysiology study). Additionally or alternatively, the system 150can be utilized as part of a treatment procedure, such as to help guidea physician to navigate a delivery device to a desired target site orregion (e.g., containing identified arrhythmogenic electrical activity).

For example, an invasive device 156, such as a catheter, can be insertedinto a patient's body 154. The device 156 includes one or moreelectrodes (e.g., unipolar leads) coupled to an invasive system 158configured to deliver electrical energy that can be localized. Thedevice 156 can apply the energy as a localization-specific signal, apacing signal or to deliver another therapy, such as to electricallyaffect tissue (e.g., providing electrical stimulation therapy, orcontrolling delivery of chemical therapy, sound wave therapy, thermaltherapy or any combination thereof).

The invasive system 158 can include a control 160 configured to controlthe signal generator 161 to apply the localization signal at one or moreelectrodes of the device 156. For example, the control 160 can controlparameters (e.g., current, voltage, repetition rate, trigger delay,sensing trigger amplitude) of the signal generator 161 for deliveringtherapy (e.g., ablation or stimulation) via the electrode(s) to one ormore location of the heart 152. The control 160 can set the therapyparameters and apply stimulation based on automatic, manual (e.g., userinput) or a combination of automatic and manual (e.g., semiautomatic)controls. The invasive system 158 can also be configured to measureelectrical activity via electrodes on the device 156, process themeasured signals and provide corresponding invasive measurement data159.

Additionally, the localization signals generated by signal generator 161and applied to electrodes on the device 156 can be measured by aplurality of sensors 164 attached to the body 154 at locations known ina three-dimensional coordinate system. The sensors 164 thus can senseelectrical activity, including signals corresponding to the appliedlocalization signals. The sensors 164 can also sense other electricalsignals, such as corresponding to real-time electrograms for thepatient's heart.

The placement of the device 156 can be guided via a localization method180, which can operate to localize the device 156 employing aminimization function, such as disclosed herein. The localization method180 can correspond to the location calculator 30, including the sensorselector 38 and calibration engine 36. For example, the localizationmethod 180 thus can evaluate a cost function by minimizing thedifference between source voltages determined for different pairs of theplurality of sensors. As disclosed herein, the sensor measurements usedby the localization method have known locations defined by geometry data172, and the sensors can be non-invasive and/or invasive. Thus, thesource voltages for non-invasive sensors are determined based onnon-invasive measurement data 170 and geometry data 172, and sourcevoltages for invasive sensors are determined based on invasivemeasurement data 159 and geometry data 172. The guidance can beautomated, semi-automated or be manually implemented based oninformation provided. During localization, the unipolar source electrodeon the device 156 can contact or not contact the patient's heart 152,endocardially or epicardially.

As a further example, the invasive system 158 can be located external tothe patient's body 154 and be configured to control therapy that isbeing delivered by the device 156. For instance, the system 158 can alsocontrol electrical signals provided via a conductive link electricallyconnected between the delivery device (e.g., one or more electrodes) 156and the system 158. One or more sensors (not shown but could be part ofthe device) can also communicate sensor information back to the system158.

The position of the device 156 in the heart 152 in three-dimensionalspace can be determined by performing localization as disclosed herein,which can be tracked intraoperatively via an output system 162 whenimplemented during a procedure. The location of the device 156 and thetherapy parameters thus can be analyzed to help control therapy.Additionally, the application of therapy (e.g, manually in response to auser input or automatically provided) can cause a timestamp or othertime identifier to be tagged (e.g., as metadata) to the measurement datato identify when the therapy is applied and trigger localization toidentify the location where the therapy is applied via the device 156.Other metadata describing the therapy (e.g., type, delivery parametersetc.) can also be stored with the measurement data.

Before, during and/or after delivering a therapy (e.g., via the system158), one or more of the non-invasive measurement system 166 or invasivesystem 158 can be utilized to acquire electrophysiology information forthe patient. The measurement system 166 can acquire navigation signalsand mapping signals simultaneously to facilitate concurrent mapping andnavigation. In the example of FIG. 6, one or more sensors 164 can beimplemented as an array or other configuration for recording patientelectrical activity. As one example, the sensors 164 can correspond to ahigh-density arrangement of body surface sensors that are distributedover a portion of the patient's torso for measuring electrical activityassociated with the patient's heart (e.g., as part of anelectrocardiographic mapping procedure). An example of a non-invasivesensor array that can be used is shown and described in theabove-incorporated International application No. PCT/US2009/063803,filed 10 Nov. 2009. Other arrangements and numbers of sensors 164 can beused. As an example, the sensors 164 can be a reduced set of sensors,which does not cover the patient's entire torso and is designed formeasuring electrical activity for a particular purpose (e.g., an arrayof electrodes specially designed for analyzing AF and/or VF) and/or formonitoring a predetermined spatial region of the heart.

Sensors located on the device 156 can be utilized separately or inconjunction with the non-invasive sensors 164 for mapping electricalactivity for an endocardial surface, such as the wall of a heartchamber, as well as for an epicardial surface. In each of such exampleapproaches for acquiring real time patient electrical information,including invasively via the device 156, non-invasively via the sensors164, or a combination of invasive and non-invasive sensing, the realtime sensed electrical signals are provided to its correspondingmeasurement system 158, 166. Similar to the invasive system 158, themeasurement system 166 can include appropriate controls and signalprocessing circuitry 168 for providing corresponding measurement data170 that describes electrical activity detected by the sensors 164. Themeasurement data 170 can include analog and/or digital information(e.g., corresponding to electrogram data acquired by sensors 164). Thus,the measurement data 159 and 170 can correspond to the measuredelectrical signals used for localization, as disclosed herein.

The control 168 can also be configured to control the data acquisitionprocess (e.g., sample rate, line filtering) for measuring electricalactivity and providing the measurement data 170. In some examples, thecontrol 168 can control acquisition of measurement data 170 separatelyfrom the invasive system operation, such as in response to a user input.In other examples, the measurement data 170 can be acquired concurrentlywith and in synchronization with specific signals applied by the signalgenerator 161 for purposes of localization. For instance, appropriatetime stamps can be utilized for indexing the temporal relationshipbetween the respective measurement data 159 and 170 and delivery oflocalization signals. The localization signals can be unique signalsapplied by the signal generator specifically to enable the localization.Additionally or alternatively, the signal generator can apply thelocalization signal, automatically or in response to a user input, fordelivering a therapy. In either example, the non-invasive measurementsystem 166 can measure the body surface electrical activity via thesensor to provide corresponding measurement data 170. The processingsystem 162 thus can perform various signal processing and transformativemethods, including a localization method 180 to localize each sourceaccording to the localization method disclosed herein.

The localization method 180 can be configured to implement any of thelocalization methods based on the measurement data 170 and/or 159 andassociated geometry data 172. The coordinates determined by thelocalization method 180 can be utilized by an output generator 188provide the output data 174. The output data 174 can represent orcharacterize the position of the device in three-dimensional space basedon coordinates of the source electrode determined according to theapproach herein. Additionally, the location (or a corresponding path)can be displayed at the spatial locations across a cardiac envelope(e.g., on an epicardial or endocardial surface of the heart 152). Theoutput generator 188 can display the location separately. In otherexamples, the location can be combined with other output data, such asto display location information on graphical map of electrical activityof the heart 152.

Since, in some examples, the measurement system 166 can measureelectrical activity of a predetermined region or the entire heartconcurrently (e.g., where the sensors 164 are evenly distributed overthe entire thorax of the patient's body 154 at predetermined locationsdefined in the geometry data 172), the measurements are spatially andtemporally consistent. Consequently, the accuracy in the resultingoutput location provided in the output data 174 can be increased whencompared to other localization techniques, such as to supply the userwith a more accurate and global information to facilitate monitoring andapplication of therapy. Additionally or alternatively, the localizationcan be continuous process and/or be synchronized with respect to theapplication of therapy provided by the system 158.

By way of further example, the electrical measurement data is obtainednon-invasively via body surface sensors 164, electrogram reconstruction186 can be programmed to compute an inverse solution and providecorresponding reconstructed electrograms based on the measurement data170 and the geometry data 172. The reconstructed electrograms thus cancorrespond to electrocardiographic activity across an envelope, and caninclude static (three-dimensional at a given instant in time) and/or bedynamic (e.g., four-dimensional map that varies over time). Examples ofinverse algorithms that can be utilized in the system 150 include thosedisclosed in U.S. Pat. Nos. 7,983,743 and 6,772,004, which areincorporated herein by reference. The EGM reconstruction 186 thus canreconstruct the body surface electrical activity measured via thesensors 164 onto a multitude of locations on an envelope (e.g., greaterthan 1000 locations, such as about 2000 locations or more). In otherexamples, the output system 162 can compute electrical activity over asub-region of the heart based on electrical activity measuredinvasively, such as via the device 156 (e.g., including a basketcatheter or other form of measurement probe).

As disclosed herein, the reconstruction envelope (e.g., cardiacenvelope) can correspond to a three-dimensional surface geometrycorresponding to a patient's heart, which surface can be epicardial orendocardial. Alternatively or additionally, the envelope can correspondto a geometric surface that resides between the epicardial surface of apatient's heart and the surface of the patient's body where the sensors164 have been positioned. Additionally, the geometry data 172 that isutilized by the electrogram reconstruction 186 can correspond to actualpatient anatomical geometry, a preprogrammed generic model or acombination thereof (e.g., a model that is modified based on patientanatomy). The location computed via the localization method 180 can beco-registered with the geometry data 172 (e.g., anatomical geometry).

Similar to as described with respect to FIG. 1, the geometry data 172may be in the form of graphical representation of the patient's torso,such as image data acquired for the patient. Such image processing(e.g., imaging processing 104) can include extraction and segmentationof anatomical features, including one or more organs and otherstructures, from a digital image set. Additionally, a location for eachof the sensors 164 used for source localization, including non-invasiveand/or invasive sensors, can be included in the geometry data 172, suchas by acquiring the image while the electrodes are disposed on thepatient and identifying the electrode locations in a coordinate systemthrough appropriate extraction and segmentation.

As another example, a first set of non-invasive sensor electrodes can besecured around the thorax before imaging (e.g., via CT or MRI), and thelocations of such electrodes can be determined via image processing.Some or all of the these sensors can then be used subsequently to locateanother set of sensors fixed within the patient's body 154, such asendocardially, epicardially or other positions fixed within the body.Other non-imaging based techniques can also be utilized to obtain theposition of the electrodes in the sensor array in the coordinate system,such as a using a digitizer, self-discovery or manual measurements,which can be stored in the geometry data 172. Once the locations of thesensors (invasive and/or non-invasive sensors) have a known location,their measurements can be selectively used by the localization method180, as disclosed herein.

The geometry data 172 can correspond to a mathematical model, such ascan be a generic model or a model that has been constructed based onimage data for the patient. Appropriate anatomical or other landmarks,including locations for the sensors 164 can be identified in thegeometry data 172 for display in conjunction with computed locationinformation for the device. The identification of such landmarks and canbe done manually (e.g., by a person via image editing software) orautomatically (e.g., via image processing techniques).

By way of further example, the geometry data 172 can be acquired usingnearly any imaging modality based on which a correspondingrepresentation of the geometrical surface can be constructed, such asdescribed herein. Such imaging may be performed concurrently withrecording the electrical activity that is utilized to generate thepatient measurement data 170 or the imaging can be performed separately(e.g., before or after the measurement data has been acquired).

The output generator 188 can generate corresponding output data 174 thatcan in turn be provide a corresponding graphical output in a display192, such as including an indication of location for the device 156. Thelocation can be displayed on graphical model of patient anatomy orsuperimposed on the electrocardiographic map 194. The location can takeother forms to provide guidance to the user, such as disclosed herein.

A graphical user interface (GUI) 190 can be employed to interact withthe processing system 162 and/or the systems 158 and/or 166. Forexample, the GUI can be used to set parameters associated with thedisplayed graphical representation, corresponding to an outputvisualization of the computed map, such as including selecting a timeinterval, a type of information that is to be presented in thevisualization and the like can be selected in response to a user input.Additionally, a user can employ the GUI 190 to selectively program oneor more parameters (e.g., models and spatial thresholds, filterparameters and the like) and/or configure the minimization functionutilized by the localization method 182 (e.g., setting a desiredresolution, associating sensor pairs, defining groups of sensors and thelike).

Additionally, in some examples, the output data 174 can be utilized bythe invasive system 158 in connection with controlling delivery oftherapy or monitoring electrical characteristics. The control 160 thatis implemented can be fully automated control, semi-automated control(partially automated and responsive to a user input) or manual controlbased on the output data 174. In some examples, the control 160 of theinvasive system 158 can utilize the output data 174 to control one ormore therapy parameters. As an example, the control 160 can controldelivery of pacing therapy to a site of the heart (e.g., epicardial orendocardial wall) based on one or more arrhythmia drivers identified. Inother examples, an individual can view the map 194 generated in thedisplay to manually control the therapy system at a location determinedbased on this disclosure. Other types of therapy and devices can also becontrolled based on the output data 174 and corresponding graphical map194.

In view of the structural and functional features described above,certain methods will be better appreciated with reference to FIG. 7.FIG. 7 depicts an example of a method 200 for localizing a source objectwithin the conductive volume. It is to be understood and appreciatedthat the illustrated actions, in other embodiments, may occur indifferent orders or concurrently with other actions. Moreover, not allfeatures illustrated in FIG. 7 may be required to implement a method. Itis to be further understood that the following method can be implementedin hardware (e.g., one or more processors, such as in a computer or anapplication specific integrated circuit), software (e.g., stored in acomputer readable medium or as executable instructions running on one ormore processors), or as a combination of hardware and software.

The method 200 can be implemented according to any of the systems ormethods disclosed herein. The method 200 begins at 202 in whichlocations of sensors are defined for a given coordinate system (e.g.,via geometry data 24 or 172). The locations of the sensors can beinvasive and/or non-invasive, as disclosed herein. At 204, a signal isapplied (e.g., by signal generator 16 or 161) to generate an electricalfield at a source. At 206, electrical signals are measured (e.g., bysensors 18 or 164 and associated measurement system 20 or 166) inresponse to applied signal.

At 208, the difference between the source voltages determined for pairsof sensors are minimized (e.g., by solving minimization function 34) toascertain a corresponding location of a source in a coordinate system.The minimization at 208 can be implemented collectively with respect toall of the sensors, assuming that sufficient homogeneous exist in theconductive volume. Alternatively, the minimization at 208 can beimplemented with respect to a plurality of different subsets ofelectrodes and the location can be determined by aggregating therespective positions that have been determined for each of therespective subsets of sensors. The minimization can be implementedaccording to Eqs. (3) and/or (4) disclosed herein, for example.

At 210, the determined location is stored in memory. The memory caninclude any local or remote memory (e.g., volatile and/or non-volatilememory) that is accessible for retrieval, such as for use by a same ordifferent computer from that implementing the method 200. The sourcelocation that is stored can thus represent spatial coordinates for thelocalized source. As mentioned, in some examples, there are multiplesources, which may be on the same or different probe, and each of suchrespective locations can be stored at 210 for each such source. At 212,the location for the object can be visualized such as in an output thatis generated and provided to a display device. For example, theidentified location can be overlaid in a graphical map of a patient'sanatomy, such as a heart or other anatomic region where the source waslocalized to reside via the method 200. By determining the location andgraphical map in a common coordinate system or (via registration ortransform) visualization of the source electrode location, as well as adevice carrying the field source for which the location was determinedat 16, is facilitated.

In view of the foregoing structural and functional description, thoseskilled in the art will appreciate that portions of the invention may beembodied as a method, data processing system, or computer programproduct. Accordingly, these portions of the present invention may takethe form of an entirely hardware embodiment, an entirely softwareembodiment, or an embodiment combining software and hardware.Furthermore, portions of the invention may be a computer program producton a computer-usable storage medium having computer readable programcode on the medium. Any suitable computer-readable medium may beutilized including, but not limited to, static and dynamic storagedevices, hard disks, optical storage devices, and magnetic storagedevices.

Certain embodiments of the invention have also been described hereinwith reference to block illustrations of methods, systems, and computerprogram products. It will be understood that blocks of theillustrations, and combinations of blocks in the illustrations, can beimplemented by computer-executable instructions. Thesecomputer-executable instructions may be provided to one or moreprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus (or a combination ofdevices and circuits) to produce a machine, such that the instructions,which execute via the processor, implement the functions specified inthe block or blocks.

These computer-executable instructions may also be stored incomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory result in an article of manufacture including instructions whichimplement the function specified in the flowchart block or blocks. Thecomputer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions specified in theflowchart block or blocks.

What have been described above are examples. It is, of course, notpossible to describe every conceivable combination of structures,components, or methods, but one of ordinary skill in the art willrecognize that many further combinations and permutations are possible.Accordingly, the invention is intended to embrace all such alterations,modifications, and variations that fall within the scope of thisapplication, including the appended claims. Where the disclosure orclaims recite “a,” “an,” “a first,” or “another” element, or theequivalent thereof, it should be interpreted to include one or more thanone such element, neither requiring nor excluding two or more suchelements. As used herein, the term “includes” means includes but notlimited to, and the term “including” means including but not limited to.The term “based on” means based at least in part on.

What is claimed is:
 1. A system comprising: a plurality of sensorsconfigured to sense electrical activity at locations distributed acrossa conductive volume, locations of each of the plurality of sensors beingpredetermined with respect to a spatial coordinate system and stored inmemory as geometry data; a source electrode positioned within theconductive volume at an unknown location that is to be determined; asignal generator to supply electrical energy to the source electrode,corresponding to a generated source voltage, which generates an electricfield, a circuit path extending from the source electrode to anelectrical ground at a position on an outer surface of the conductivevolume, which is coupled to the signal generator; and a locationcalculator implemented as instructions executable by a computerprocessor in the system, the location calculator configured to computethe location of the source electrode by minimizing a difference betweendetermined source voltages that are determined for multiple pairs of theplurality of sensors, each of the determined source voltages beingdetermined for each respective one of the plurality of sensors based ona respective sensor measurement of voltage in response to the electricfield and based on relative locations of the sensors determined from thegeometry data.
 2. The system of claim 1, wherein the location calculatoris configured to compute the location of the source electrode based onthe sensor measurements acquired concurrently for each of the pluralityof sensors in response to the electric field.
 3. The system of claim 2,wherein the plurality of sensors includes at least three electrodesdistributed across the conductive volume.
 4. The system of claim 1,wherein the geometry data specifying the predetermined location of eachof the plurality of sensors comprises information generated by at leastone of: self-discovery, wherein the spatial distribution of the sensorswith respect to each other or a neutral point is computed based on aprogrammed sequence of current or voltage applied among the sensors,based on imaging data, or a digitizer.
 5. The system of claim 1, furthercomprising a channel integrity detector implemented as instructionsexecutable by a computer processor in the system, the channel integritydetector configured to identify one or more channels for exclusion fromsubsequent analysis based on one or more of correlation of a channel'ssignal with respect to signals of spatially neighboring channels,amplitude of the channel's signal, the channel being a short circuit,and/or the channel being an open circuit, the geometry data and thesensor measurements for each channel identified for exclusion being madeunavailable for the computation by the location calculator.
 6. Thesystem of claim 1, further comprising volume impedance data stored inthe memory to characterize impedance of the conductive volume, thelocation calculator accounting for variations in the impedance of theconductive volume based on the volume impedance data.
 7. The system ofclaim 6, further comprising an impedance calculator implemented asinstructions executable by a computer processor in the system, theimpedance calculator configured to generate the volume impedance databased on electric fields sensed by the plurality of sensors in responseto the electric field applied to the conductive volume.
 8. The system ofclaim 1, further comprising a calibration engine implemented asinstructions executable by a computer processor in the system, thecalibration engine configured to group the plurality of sensors intomultiple subsets of the plurality of sensors by assigning each sensor toone of the subsets, the location calculator computing the location ofthe source electrode by minimizing the difference between sourcevoltages determined for respective sensor pairs in at least one of thesubsets of the plurality of sensors.
 9. The system of claim 8, whereinthe location calculator is configured to compute the location of thesource electrode by aggregating source location values separatelycomputed from corresponding sensor measurements acquired from at leasttwo of the subsets of the plurality of sensors.
 10. The system of claim8, wherein the calibration engine is configured to automaticallydetermine the assignment of the plurality of sensors to the multiplesubsets of the plurality of sensors based on at least one of the volumeimpedance data, the geometry data or imaging data.
 11. The system ofclaim 8, wherein the calibration engine is configured to determine theassignment of the plurality of sensors to the multiple subsets of theplurality of sensors in response to a user input selecting which sensorsto include in each of the respective subsets of the plurality ofsensors.
 12. The system of claim 1, wherein the location calculatorfurther comprises a sensor selector implemented as instructionsexecutable by a computer processor in the system, the sensor selectorconfigured to select at least three different pairs of sensors from theplurality of sensors, the location calculator computing the positionbased on the sensor measurements from the selected pairs of sensors. 13.The system of claim 12, further comprising a channel integrity detectorto identify for exclusion from subsequent analysis channels based on oneor more of correlation of a channel's signal with respect to signals ofspatially neighboring channels, amplitude of the channel's signal, thechannel being a short circuit, and/or the channel being an open circuit,to provide a remaining available subset of the plurality of sensors fromwhich the sensor selector selects each of the selected pairs of sensors.14. The system of claim 12, wherein the location calculator furthercomprises a homogeneity calculator implemented as instructionsexecutable by a computer processor in the system, the homogeneitycalculator configured to determine an indication of homogeneity of theconductive volume between respective pairs of sensors, the sensorselector selecting each of the selected pairs of sensors into arespective subset of sensors based on the indication of homogeneity. 15.The system of claim 14, further comprising an impedance calculatorimplemented as instructions executable by a computer processor in thesystem, the impedance calculator configured to determine impedance datarepresenting impedance through the conductive volume, the homogeneitycalculator determining the indication of homogeneity of the conductivevolume based on the impedance data.
 16. A method comprising: applying alocalization signal to a source electrode positioned within a conductivevolume and a ground electrode at a known location with respect to theconductive volume, the known location of the ground electrode beingstored in memory as part of geometry data; sensing electrical activityat a plurality of sensor electrodes distributed across the conductivevolume, a location of each of the plurality of sensor electrodes beingpredetermined with respect to a spatial coordinate system and stored inthe memory as part of the geometry data, the electrical activity sensedat each of the plurality of sensor electrodes in response to the appliedlocalization signal being stored in the memory as electrical measurementdata; and computing the location of the source electrode by minimizing adifference between respective pairs of determined source voltagesdetermined for the plurality of sensor electrodes, the determined sourcevoltage for each of the respective sensor electrodes being based on thelocalization signal applied to the source electrode as provided in theelectrical measurement data and also based on relative locations of thesensor electrodes determined from the geometry data.
 17. The method ofclaim 16, wherein computing the location of the source electrode furthercomprises: computing the source voltage associated based on theelectrical activity sensed at each of the plurality of sensor electrodesand as a function of the location of the respective sensor electrode andthe location of the ground electrode; selecting each of the pairs of thesensor electrodes; and computing the difference between the computedsource voltage for each of the selected pairs of the sensor electrodes.18. The method of claim 16, wherein prior to computing the location ofthe source electrode, the method further comprises: grouping theplurality of sensor electrodes into a plurality of subsets of the sensorelectrodes by assigning each sensor electrode to one of the plurality ofsubsets; computing the location of the source electrode being separatelyfor respective sensor pairs in at least two of the plurality of subsetsof the sensor electrodes; and combining the location of the sourceelectrode computed for each of the plurality of subsets of the sensorelectrodes.
 19. The method of claim 18, further comprising, prior tocomputing the location of the source electrode, calibrating aminimization function that is used in the computing, the calibrationbeing implemented based on at least one of the geometry data, theelectrical measurement data, channel detection data or in response to auser input.
 20. One or more non-transitory computer-readable mediastoring data and instructions executable by a processor, wherein thedata comprises: geometry data representing locations of each of aplurality of sensors at locations distributed across an outer surface ofa conductive volume; and measurement data representing sensed electricalmeasurements for each of the plurality of sensors, the sensed electricalmeasurements corresponding to an electric field generated in response toapplying electrical energy to a source electrode located within theconductive volume, and wherein the instructions comprise a locationcalculator to compute a location of the source electrode within theconductive volume by minimizing a difference between determined sourcevoltages that are determined for multiple pairs of the plurality ofsensors, each of the determined source voltages being determined foreach of the respective plurality of sensors based on the measurementdata including the sensed electrical measurements as well as relativelocations of the plurality of sensors determined from the geometry data.